Application and clinical impact of the RESIST-4 O.K.N.V. rapid diagnostic test for carbapenemase detection in blood cult

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Application and clinical impact of the RESIST-4 O.K.N.V. rapid diagnostic test for carbapenemase detection in blood cultures and clinical samples Sophie Roth 1 & Fabian K. Berger 1 & Andreas Link 2 & Anna Nimmesgern 1 & Philipp M. Lepper 3 & Niels Murawski 4 & Jörg T. Bittenbring 4 & Sören L. Becker 1 Received: 13 July 2020 / Accepted: 24 August 2020 # The Author(s) 2020

Abstract Invasive infections caused by carbapenemase-producing bacteria are associated with excess mortality. We applied a rapid diagnostic test (RDT) on clinical samples with an elevated likelihood of carbapenemase-producing bacteria and documented its impact on antibiotic treatment decisions. Among 38 patients, twelve tested positive for infections caused by carbapenemaseproducing bacteria (31.6%), mainly in blood cultures. KPC (n = 10) was more frequent than OXA-48 (n = 2). RDT-based carbapenemase detection led to a treatment modification to ceftazidime/avibactam-containing regimens in all patients before detailed antibiotic testing results became available. Eleven patients (92%) survived the acute infection, whereas one patient with a ceftazidime/avibactam- and colistin-resistant OXA-48-positive isolate died. Keywords Antibiotics . Clinical microbiology . Diagnostic stewardship . Enterobacterales . Escherichia coli . Klebsiella pneumoniae . Treatment

Introduction Increasing antimicrobial resistance is among the biggest threats to global health. Resistance in gram-negative bacteria is particularly worrying, e.g. Enterobacterales and non-fermentative bacteria that produce carbapenemases, leading to nonsusceptibility to all carbapenem antibiotics. Carbapenemasecarrying plasmids are easily transferred to other bacteria through horizontal gene transfer. A significant increase in carbapenemase-producing bacteria such as Klebsiella pneumoniae in high-income countries is associated with an excess mortality of up to 50% [1], with inadequate empirical * Sören L. Becker [email protected] 1

Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany

2

Department of Internal Medicine III, Saarland University, Homburg, Germany

3

Department of Internal Medicine V, Saarland University, Homburg, Germany

4

Department of Internal Medicine I, Saarland University, Homburg, Germany

treatment and delayed diagnosis of carbapenem resistance being major contributing factors [2, 3]. It is pivotal to reduce the time to appropriate antimicrobial treatment by early detection of multiresistant pathogens and to elucidate the underlying resistance mechanism to switch treatment, e.g. to new beta-lactam/ beta-lactamase inhibitor combination antibiotics such as ceftazidime/avibactam or the siderophore cephalosporin cefiderocol with a broad activity against frequently isolated carbapenemases in Europe, i.e. KPC and OXA-48 [4]. Recently, immunochromatographic rapid diagnostic tests (RDTs) to detect different carbapenemases in culture-grown bacteria within 10–20 min have been introduced. In the present study, we investigated the di